PROJECT SUMMARY/ ABSTRACT Mosquito-transmitted parasitic diseases are among the major causes of mortality and morbidity in the world. Recent dramatic increases in the incidence of mosquito-borne diseases, like Malaria, Chikungunya, Dengue and Zika, and the wide-spread resistance of mosquitoes to insecticides underscores the need for new approaches for insect control based on mosquito-specific agents. The discovery of such mosquito-specific control agents depends on basic research on the biology of mosquitoes. Nutritional and hormonal regulation of reproduction is a critical component of female fitness, and therefore of vectorial capacity. Interventions that focus on reducing fitness or interfering with reproduction should be established based on a clear understanding of reproductive biology. Depending on nutrient availability, female mosquitoes constantly adjust their reproductive output, mostly by ovarian follicular resorption by apoptosis. The ?fate? of an individual follicle is dynamically changed based on its nutritional status. Successful follicles remain competent or ?viable? (follicles that later will develop into an egg), while outcompeted are resorbed or become ?unviable? (those that could be resorbed by apoptosis anytime during a later stage of development). We would like to test the hypothesis that the developmental fate of all the follicles remains ?dynamically? sensitive to changes in nutrition during oogenesis. Understanding the molecular and biochemical bases of follicle viability is a central aspect in mosquito reproductive biology. In this proposal, we would like to start addressing three fundamental questions: (1) Can we establish molecular profiles that help us to discriminate viable and unviable follicle phenotypes, and consequently predict a follicle ultimate fate? (2) Can we reveal the molecular bases of the dynamic changes in follicle phenotype? (3) Do females have the ability to move nutrients out of the follicles and reverse previous reproductive allocations? To accomplish this goal, we will pursue the following two specific aims: 1) To characterize the lipid metabolic profile of viable and unviable follicles and 2) To understand the molecular bases of the dynamic changes in follicular lipid phenotypes during oogenesis. To complete these aims, we are proposing an integrative approach that brings together excellent mosquito reproductive fitness experimental models with new and state-of-the- art mass spectrometry imaging (MSI) based strategies; aiming to identify, quantify and map the spatial distribution of biomolecules in mosquito ovaries. Completing the aims of this proposal might provide opportunities for identifying targets for novel specific chemical and/or genetic strategies to control mosquitoes. Furthermore, we are developing new state of the art innovative mosquito MSI applications that will benefit other members of the vector biology community.